The Control of Mammalian Oocyte Maturation

Work in this laboratory focuses on chemical mediators and mechanisms involved in the control of meiotic maturation in the mammalian oocyte. We have identified purines within the ovarian follicle that play an important role in the meiotic-arresting and –inducing mechanisms that regulate oocyte maturation. We have also examined how energy substrates affect meiosis, including their metabolic routes and interaction with purine metabolic pathways. Because of the importance of glucose in meiotic control, we have tested the effects of experimentally induced diabetes on oocyte maturation and find serious defects in metabolism and meiotic regulation. Cyclic adenosine monophosphate, or cAMP, is an important regulatory molecule that exerts both positive and negative actions on meiotic maturation. We are currently investigating how fluctuations in the levels of this important second messenger within the oocyte relate to meiotic regulation. A recent subject of interest is the possible involvement of the stress-response kinase, AMP-activated protein kinase (AMPK), in meiotic control. We have reported that AMPK is present in mouse oocytes and that its activation is associated with the meiosis-inducing action of the adenosine analog, AICA riboside. Recent results indicate the AMPK plays a physiological role in regulating oocyte maturation in mice. Since AMPK activation leads to stimulation of fatty acid oxidation, we are currently investigating to what extent this metabolic pathway is involved in meiotic induction in mice. Additional studies center on a possible role for AMPK in meiotic induction induced by physical, chemical and metabolic stress as well as the importance of AMPK throughout oocyte maturation and preimplantation embryo development. We have also begun a careful comparison of meiotic regulation in mouse and rat oocytes, since initial work indicates profound differences between the two species.